Another step toward final call on Remdesivir efficacy as a treatment for hospitalized COVID-19 patients: a multicenter open-label trial

Hosseini et al., medRxiv, doi:10.1101/2021.08.13.21261992 , Aug 2021

https://c19early.org/hosseini2.html

Single arm remdesivir trial with 145 hospitalized patients showing no statistically significant difference between "early" and "late" administration, however the treatment delays may be better described as late and very late. The text of the paper defines early and late as less than or more than 7 days from symptom onset, however the CONSORT diagram says during or after 7 days post admission.

Gérard, Zhou, Wu, Kamo, Choi, Kim show increased risk of acute kidney injury with remdesivir. Leo, Briciu, Muntean, Petrov show increased risk of liver injury with remdesivir.

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1. Gérard et al., Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145.wiley.com, doi.org.

2. Zhou et al., Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis, Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679.frontiersin.org, doi.org.

3. Wu et al., Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS, Frontiers in Pharmacology, doi:10.3389/fphar.2022.692828.frontiersin.org, doi.org.

4. Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.iiarjournals.org, doi.org.

5. Choi et al., Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0.sciencedirect.com, doi.org.

6. Kim et al., Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study, Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043.wiley.com, doi.org.

7. Leo et al., Hepatocellular liver injury in hospitalized patients affected by COVID-19: Presence of different risk factors at different time points, Digestive and Liver Disease, doi:10.1016/j.dld.2021.12.014.sciencedirect.com, doi.org.

8. Briciu et al., Evolving Clinical Manifestations and Outcomes in COVID-19 Patients: A Comparative Analysis of SARS-CoV-2 Variant Waves in a Romanian Hospital Setting, Pathogens, doi:10.3390/pathogens12121453.mdpi.com, doi.org.

9. Muntean et al., Effects of COVID-19 on the Liver and Mortality in Patients with SARS-CoV-2 Pneumonia Caused by Delta and Non-Delta Variants: An Analysis in a Single Centre, Pharmaceuticals, doi:10.3390/ph17010003.mdpi.com, doi.org.

10. Petrov et al., The Effect of Potentially Hepatotoxic Medicinal Products on Alanine Transaminase Levels in COVID-19 Patients: A Case–Control Study, Safety and Risk of Pharmacotherapy, doi:10.30895/2312-7821-2025-458.risksafety.ru, doi.org.

Hosseini et al., 13 Aug 2021, preprint, 15 authors.

This Paper Remdesivir All

Abstract: medRxiv preprint doi: https://doi.org/10.1101/2021.08.13.21261992; this version posted August 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . Title: Another step toward final call on Remdesivir efficacy as a treatment for hospitalized COVID-19 patients: a multicenter open-label trial Running title: Remdesivir efficacy in COVID-19 treatment Authors: Hamed Hosseini1, Anahita Sadeghi2, Payam Tabarsi3, Azin Etemadimanesh4, Ilad Alavi Darazam3, Nasser Aghdami4, Saeed Kalantari5, Mehrdad Hasibi4, Azar Hadadi4, Farhang Babamahmoodi6, Mansooreh Momen-Heravi7, Ahmad Hormati8,9, Yunes Panahi10, Rozita Khodashahi11, Mohammadreza Salehi4* 1. Center for Research and Training in Skin Disease and Leprosy, Tehran University of Medical Sciences. 2. Department of Internal Medicine, Tehran University of Medical Sciences, Tehran, Iran. 3. Department of Infectious Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Department of Infectious Disease, Tehran University of Medical Science, Tehran, Iran. 5. Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran 6. Antimicrobial Resistance Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran 7. Department of infectious diseases, faculty of medicine, Kashan university of medical sciences, Kashan, Iran. 8. Gastroenterology and Hepatology Disease Research Center, Oom university of medical sciences, Iran. NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2021.08.13.21261992; this version posted August 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . 9. Gastrointestinal and Liver Diseases Research Center, Iran university of medical sciences, Tehran, Iran. 10. Pharmacotherapy Department, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran 11. Department of Infectious disease and tropical medicine, Faculty of Medicine, Mashhad university of medical sciences, Mashhad, Iran. Corresponding author: Mohammadreza Salehi M.D., Department of Infectious Disease, Tehran University of Medical Sciences. Imam Khomeini hospital complex, Gharib St., Tehran, Iran. Email: salehi.mohamad3@gmail.com , ORCID: 0000-0002-1987-5929, Cellphone: +989123159842 Declaration of interests: Hereby, all authors of this study declare no conflict of interests before, during, and after the study was done. Acknowledgments: Our sincere thanks to Professor Reza Malekzadeh who coordinated and supervised the project. We express our gratitude to the Digestive Diseases Research Institute (DDRI), Tehran University of Medical Sciences. Conducting the study would not have been possible without the efforts of the DDRI team. The authors also would like to express their gratitude for all care workers and patients in study hospitals. This study has been funded and supported by Tehran University of Medical Sciences (TUMS); Grant no. 99-1-97-47143. medRxiv preprint doi:..

DOI record: { "DOI": "10.1101/2021.08.13.21261992", "URL": "http://dx.doi.org/10.1101/2021.08.13.21261992", "abstract": "AbstractIntroductionAfter emerging the global pandemic of SARS-CoV2 some preliminary studies demonstrated the efficacy of antiviral treatments. But shortly thereafter, inconsistencies in the results of further clinical trials raised doubts on the efficacy of these agents. In this study, we aimed to evaluate the effect of Remdesivir on hospitalized COVID-19 patients’ outcomes.Material and methodsThis study was an open-label, single-armed, clinical trial on hospitalized patients diagnosed with COVID-19 who had progressive respiratory symptoms despite receiving standard care. All patients received Remdesivir and their characteristics, outcomes, time of treatment initiation, and respiratory support stages during hospitalization were registered and followed up for 14 days.Results145 patients with the mean age of 52.89 ± 1.12 years enrolled in this study, 38 (26.2%) died at the end of 14 days period. The mean time interval from the onset of the symptoms to antiviral treatment was 10.63±0.56 days. Thirty deceased patients (78.9%) were men, showing 2.8 times higher mortality chance compared to women (ORadj=2.77; 95%CI=1.08-7.09). The type of respiratory support on the first day of treatment initiation showed a significantly lower mortality chance in patients receiving O2only than those who needed non-invasive and/or mechanical ventilation (ORadj=3.91; 95%CI=1.64-9.32). The start time (early vs late administration) and duration (less or more than 7 days) of antiviral treatment had no statistically significant association with mortality or ventilation escalation among the patients (p-value > 0.05).ConclusionIn this study, we showed that Remdesivir probably is not effective on the outcome of hospitalized COVID-19 patients.", "accepted": { "date-parts": [ [ 2021, 8, 13 ] ] }, "author": [ { "ORCID": "http://orcid.org/0000-0003-2368-6749", "affiliation": [], "authenticated-orcid": false, "family": "Hosseini", "given": "Hamed", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0001-9564-4631", "affiliation": [], "authenticated-orcid": false, "family": "Sadeghi", "given": "Anahita", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-8932-5420", "affiliation": [], "authenticated-orcid": false, "family": "Tabarsi", "given": "Payam", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6923-0133", "affiliation": [], "authenticated-orcid": false, "family": "Etemadimanesh", "given": "Azin", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-4440-335X", "affiliation": [], "authenticated-orcid": false, "family": "Darazam", "given": "Ilad Alavi", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-5390-7878", "affiliation": [], "authenticated-orcid": false, "family": "Aghdami", "given": "Nasser", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-9896-4139", "affiliation": [], "authenticated-orcid": false, "family": "Kalantari", "given": "Saeed", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-8120-6400", "affiliation": [], "authenticated-orcid": false, "family": "Hasibi", "given": "Mehrdad", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-5080-6887", "affiliation": [], "authenticated-orcid": false, "family": "Hadadi", "given": "Azar", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-4239-9569", "affiliation": [], "authenticated-orcid": false, "family": "Babamahmoodi", "given": "Farhang", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-8528-8271", "affiliation": [], "authenticated-orcid": false, "family": "Momen-Heravi", "given": "Mansooreh", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-1322-1318", "affiliation": [], "authenticated-orcid": false, "family": "Hormati", "given": "Ahmad", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-2504-8356", "affiliation": [], "authenticated-orcid": false, "family": "Panahi", "given": "Yunes", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6514-7308", "affiliation": [], "authenticated-orcid": false, "family": "Khodashahi", "given": "Rozita", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-1987-5929", "affiliation": [], "authenticated-orcid": false, "family": "Salehi", "given": "Mohammadreza", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2021, 8, 13 ] ], "date-time": "2021-08-13T20:15:19Z", "timestamp": 1628885719000 }, "deposited": { "date-parts": [ [ 2023, 1, 7 ] ], "date-time": "2023-01-07T10:29:03Z", "timestamp": 1673087343000 }, "group-title": "Infectious Diseases (except HIV/AIDS)", "indexed": { "date-parts": [ [ 2023, 8, 14 ] ], "date-time": "2023-08-14T09:52:51Z", "timestamp": 1692006771192 }, "institution": [ { "name": "medRxiv" } ], "is-referenced-by-count": 3, "issued": { "date-parts": [ [ 2021, 8, 13 ] ] }, "link": [ { "URL": "https://syndication.highwire.org/content/doi/10.1101/2021.08.13.21261992", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "246", "original-title": [], "posted": { "date-parts": [ [ 2021, 8, 13 ] ] }, "prefix": "10.1101", "published": { "date-parts": [ [ 2021, 8, 13 ] ] }, "publisher": "Cold Spring Harbor Laboratory", "reference": [ { "article-title": "WHO declares COVID-19 a pandemic", "first-page": "157", "issue": "1", "journal-title": "Acta bio-medica: Atenei Parmensis", "key": "2021081607550690000_2021.08.13.21261992v1.1", "volume": "91", "year": "2020" }, { "DOI": "10.1016/S1473-3099(20)30120-1", "doi-asserted-by": "publisher", "key": "2021081607550690000_2021.08.13.21261992v1.2" }, { "DOI": "10.7326/M20-2911", "doi-asserted-by": "crossref", "key": "2021081607550690000_2021.08.13.21261992v1.3", "unstructured": "Jalili, M. , et al., Characteristics and mortality of hospitalized patients with COVID-19 in Iran: a National Retrospective Cohort Study. 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Late treatment
is less effective

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